crossing96/oncoscreening huggingface dataset:
Italian pool of asbestos workers cohorts: asbestos related mortality by industrial sector and cumulative exposure.	OBJECTIVE: Italy has been a large user of asbestos and asbestos containing materials until the 1992 ban. We present a pooled cohort study on long-term mortality in exposed workers. METHODS: Pool of 43 Italian asbestos cohorts (asbestos cement, rolling stock, shipbuilding, glasswork, harbors, insulation and other industries). SMRs were computed by industrial sector for the 1970-2010 period, for the major causes, using reference rates by age, sex, region and calendar period. RESULTS: The study included 51 801 subjects (5741 women): 55.9% alive, 42.6% died (cause known for 95%) and 1.5% lost to follow-up. Asbestos exposure was estimated at the plant and period levels. Asbestos related mortality was significantly increased. All industrial sectors showed increased mortality from pleural malignancies, and most also from peritoneal and lung cancer and asbestosis, with exposure related trend. Increased mortality was also observed for ovarian cancer and for bladder cancer. DISCUSSION: The study confirmed the increased risk for cancer of the lung, ovary, pleura and peritoneum but not of the larynx and the digestive tract. A large increase in mortality from asbestosis was observed.	bladder
The impact of previous cancer on overall survival of bladder cancer patients and the establishment of nomogram for overall survival prediction.	To investigate the role of previous cancer on overall survival in patients with bladder cancer (BCa) and to establish an effective prognostic tool for individualized overall survival prediction.A total of 78,660 patients diagnosed with BCa between 2000 and 2013 were selected from the Surveillance, Epidemiology, and End Results (SEER) database, among which 8915 patients had a history of other cancers. We compared the overall survival between patients with and without previous cancer after propensity score matching and we further established a nomogram for overall survival prediction.Univariate and multivariate Cox analyses were used to determine independent prognostic factors. The calibration curve and concordance index (C-index) were used to assess the accuracy of the nomogram. Cox proportional hazards models and Kaplan-Meier analysis were used to compare survival outcomes.BCa patients with previous cancer had worse overall survival compared with those without previous cancer (HR = 1.37; 95%CI = 1.32-1.42, P < .001). Cancers in lung prior to BCa had the most adverse impact on overall survival (HR = 2.35; 95%CI = 2.10-2.63; P < .001), and the minimal impact was located in prostate (HR = 1.16; 95%CI = 1.10-1.22; P < .001) for male and in gynecological (HR = 1.15; 95%CI = 1.02-1.30; P = .027) for female. The shorter interval time between 2 cancers and the higher stage of the previous cancer development, the higher risk of death. Age, race, sex, marital status, surgery, radiation, grade, stage, type of previous cancer as the independent prognostic factors were selected into the nomogram. The favorable calibration curve and C-index value (0.784, 95%CI = 0.782-0.786) indicated the nomogram could accurately predict the 1-, 3-, and 5-year overall survival rate of BCa patients.Previous cancer has a negative impact on the overall survival of BCa patients and requires more effective clinical management. The nomogram provides accurate survival prediction for BCa patients and might be helpful for clinical treatment selection and follow-up strategy adjustment.	bladder
Relevance of iNOS expression in tumor growth and maintenance of cancer stem cells in a bladder cancer model.	The expression of inducible nitric oxide (NO) synthase (iNOS) in human bladder cancer (BC) is a poor prognostic factor associated with invasion and tumor recurrence. Here, we evaluated the relevance of iNOS expression in BC progression and in cancer stem cell (CSC) maintenance in a murine BC model. Also, iNOS expression and CSC markers were analyzed in human BC samples. iNOS inhibitors (L-NAME or 1400W) or shRNA were used on murine BC model with different iNOS expressions and invasiveness grades: MB49 (iNOS+, non-muscle invasive (NMI)) and MB49-I (iNOS++, muscle invasive (MI)), in order to analyzed cell proliferation, tumor growth, angiogenesis, number of CSC, and pluripotential marker expression. iNOS, SOX2, Oct4, and Nanog expressions were also analyzed in human BC samples by qPCR and immunohistochemistry. iNOS inhibtion reduced parameters associated with tumor progression and reduced the number of CSC, wich resulted higher in MB49-I than in MB49, in concordance with the higher expression of SOX2, Oct4, and Nanog. The expression of SOX2 was notoriously diminished, when iNOS was inhibited only in the MI cell line. Similar results were observed in human samples, where MI tumors expressed higher levels of iNOS and pluripotential genes, in comparison to NMI tumors with a positive correlation between those and iNOS, suggesting that iNOS expression is associated with CSC. iNOS plays an important role in BC progression and CSC maintenance. Its inhibition could be a potential therapeutic target to eradicate CSC, responsible for tumor recurrences. KEY MESSAGES: • iNOS expression is involved in bladder tumor development, growth, and angiogenesis. • iNOS expression is involved in bladder cancer stem cell generation and maintenance, playing an important role regulating their self-renewal capacity, especially in muscle invasive murine bladder cancer cells. • iNOS expression is higher in human muscle invasive tumors, in association with a high expression of pluripotential genes, especially of SOX2.	bladder
lncRNA OTUD6B-AS1 Exacerbates As(2)O(3)-Induced Oxidative Damage in Bladder Cancer via miR-6734-5p-Mediated Functional Inhibition of IDH2.	Arsenic trioxide (As(2)O(3)) is a promising effective chemotherapeutic agent for cancer treatment; however, how and through what molecular mechanisms the oxidative damage of As(2)O(3) is controlled remains poorly understood. Recently, the involvement of dysregulated long noncoding RNA ovarian tumor domain containing 6B antisense RNA1 (lncRNA OTUD6B-AS1) in tumorigenesis is established. Here, for the first time, we characterize the regulation of As(2)O(3) in the oxidative damage against bladder cancer via lncRNA OTUD6B-AS1. As(2)O(3) could activate lncRNA OTUD6B-AS1 transcription in bladder cancer cells, and these findings were validated in a xenograft tumor model. Functional assays showed that lncRNA OTUD6B-AS1 dramatically exacerbated As(2)O(3)-mediated oxidative damage by inducing oxidative stress. Mechanistically, As(2)O(3) increased levels of metal-regulatory transcription factor 1 (MTF1), which regulates lncRNA OTUD6B-AS1, in response to oxidative stress. Further, lncRNA OTUD6B-AS1 inhibited mitochondrial NADP(+)-dependent isocitrate dehydrogenase 2 (IDH2) expression by stabilizing miR-6734-5p, which contributed to cytotoxicity by enhancing oxidative stress. Together, our findings offer new insights into the mechanism of As(2)O(3)-induced oxidative damage and identify important factors in the pathway, As(2)O(3)/lncRNA OTUD6B-AS1/miR-6734-5p/IDH2, expanding the knowledge of activity of As(2)O(3) as cancer treatment.	bladder
NONO Inhibits Lymphatic Metastasis of Bladder Cancer via Alternative Splicing of SETMAR.	Bladder cancer patients with lymph node (LN) metastasis have an extremely poor prognosis and no effective treatment. The alternative splicing of precursor (pre-)mRNA participates in the progression of various tumors. However, the precise mechanisms of splicing factors and cancer-related variants in LN metastasis of bladder cancer remain largely unknown. The present study identified a splicing factor, non-POU domain-containing octamer-binding protein (NONO), that was significantly downregulated in bladder cancer tissues and correlated with LN metastasis status, tumor stage, and prognosis. Functionally, NONO markedly inhibited bladder cancer cell migration and invasion in vitro and LN metastasis in vivo. Mechanistically, NONO regulated the exon skipping of SETMAR by binding to its motif, mainly through the RRM2 domain. NONO directly interacted with splicing factor proline/glutamine rich (SFPQ) to regulate the splicing of SETMAR, and it induced metastasis suppression of bladder cancer cells. SETMAR-L overexpression significantly reversed the metastasis of NONO-knockdown bladder cancer cells, both in vitro and in vivo. The further analysis revealed that NONO-mediated SETMAR-L can induce H3K27me3 at the promotor of metastatic oncogenes and inhibit their transcription, ultimately resulting in metastasis suppression. Therefore, the present findings uncover the molecular mechanism of lymphatic metastasis in bladder cancer, which may provide novel clinical markers and therapeutic strategies for LN-metastatic bladder cancer.	bladder
"Advances in urologic oncology ""OncoForum"": The best of 2019."	OBJECTIVE: Review the latest evidence on urologic oncology on kidney, bladder and prostate tumors. METHODS: Abstracts on kidney, bladder and prostate cancer presented at the 2019 congresses (EAU, AUA, ASCO and ESMO) and the publications with the greatest impact in this period, with the highest evaluation by the OncoForum committee, are reviewed. RESULTS: In patients with metastatic kidney cancer, regimens including immunotherapy (nivolumab + ipilimumab, pembrolizumab) have been shown to be superior to sunitinib in terms of survival. In patients with non-muscle invasive bladder cancer, pembrolizumab has been shown to be an effective alternative in those refractory to bacillus Calmette-Guérin, while in patients with metastatic urothelial cancer, third-line enfortumab vedotin achieved a significant response rate (44%). In patients with localized prostate cancer (PCa), ultrafractionated external radiotherapy did not show any greater acute toxicity than fractionated or hypofractionated radiotherapy. The benefit of enzalutamide and apalutamide associated with castration has been confirmed in M1 PCa patients, regardless of disease volume. In patients with castration-resistant M0 PCa, treatment with enzalutamide, apalutamide or darolutamide has been associated with a delay in the occurrence of metastasis and prolonged survival. Cabazitaxel has demonstrated a survival benefit in patients with metastatic CRPC, while olaparib showed anti-tumor activity after chemotherapy in those tumors with mutations in DNA repair genes. CONCLUSIONS: These data show the implementation of immunotherapy as a novel alternative against renal and bladder cancer. The arrival of new agents for advanced urothelial carcinoma should be highlighted, and the efficacy of enzalutamide and apalutamide in de novo metastatic prostate cancer is established. In metastatic CRPC, cabazitaxel and olaparib (targeting mutations) are promising therapeutic options.	bladder
Impact of symptomatic recurrence on oncological outcomes in patients with primary high-risk non-muscle-invasive bladder cancer.	OBJECTIVES: To evaluate the impact of symptomatic recurrence on oncological outcomes in patients with primary high-risk non-muscle invasive bladder cancer (NMIBC) who underwent transurethral resection of bladder tumor (TURBT). MATERIALS AND METHODS: We retrospectively evaluated 428 patients with primary high-risk NMIBC who underwent TURBT from November 1993 to April 2019. Of the 428 patients, 140 had experienced recurrence at any site and were divided into 2 groups: patients who had experienced recurrence detected by the surveillance (asymptomatic group) and patients who had experienced recurrence detected by a symptom-driven investigation (symptomatic group). Background-adjusted multivariable analyses with the inverse probability of treatment weighting method were performed to evaluate the impact of symptomatic recurrence on cancer-specific survival and overall survival after first recurrence in patients who had experienced recurrence. Moreover, multivariable analysis was performed to identify predictive factors of symptomatic recurrence in the entire cohort. RESULTS: Median age and follow-up periods were 72 (interquartile range [IQR] 64-79) years and 55 (IQR 29-96) months, respectively. Of the 140 patients who experienced recurrence, 106 (76%) were diagnosed by the surveillance (asymptomatic group) and 34 (24%) were diagnosed by a symptom-driven investigation (symptomatic group). In the background-adjusted multivariable analyses with the inverse probability of treatment weighting model, symptomatic recurrence was significantly associated with shorter cancer-specific survival along with shorter overall survival after first recurrence. In the multivariable analysis, only tumor grade was selected as a significant predictive factor of symptomatic recurrence after TURBT. CONCLUSIONS: Symptomatic recurrence was significantly associated with poor oncological outcomes in patients with primary high-risk NMIBC. Patients with grade 3 tumors may require more intensive surveillance after TURBT.	bladder
VI-RADS for Bladder Cancer: Current Applications and Future Developments.	Bladder cancer (BCa) is among the ten most frequent cancers globally. It is the tumor with the highest lifetime treatment-associated costs, and among the tumors with the heaviest impacts on postoperative quality of life. The purpose of this article is to review the current applications and future perspectives of the Vesical Imaging Reporting and Data System (VI-RADS). VI-RADS is a newly developed scoring system aimed at standardization of MRI acquisition, interpretation, and reporting for BCa. An insight will be given on the BCa natural history, current MRI applications for local BCa staging with assessment of muscle invasiveness, and clinical implications of the score for disease management. Future applications include risk stratification of nonmuscle invasive BCa, surveillance, and prediction and monitoring of therapy response. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY STAGE: 2.	bladder
Overview of the clinical use of erdafitinib as a treatment option for the metastatic urothelial carcinoma: where do we stand.	INTRODUCTION: Erdafitinib is the first orally administered pan-fibroblast growth factor receptor (FGFR) kinase inhibitor approved by the Food and Drug Administration (FDA). AREAS COVERED: Specifically binding to FGFR family (FGFR-1 to FGFR-4), erdafitinib leads to reduced cell signaling and cellular apoptosis. Coupled with the ability to bind to vascular endothelial growth factor 2 (VEGFR-2), KIT, Fms-related tyrosine kinase 4 (FLT4), platelet-derived growth factor receptor α and β (PDGFR-α and PDGFR-β), RET and colony-stimulating factor 1 receptor (CSF-1 R), erdafitinib has further reported antitumor features causing cell killing. EXPERT OPINION: In this review, we provide a comprehensive overview of erdafitinib chemical structure, pharmacologic properties, and current knowledge of clinical efficacy in the treatment of locally advanced or metastatic urothelial carcinoma. This treatment, recently approved in the U.S., is available for adult patients harboring FGFR2/FGFR3 genetic alterations who progressed within 12 months of an adjuvant or neoadjuvant chemotherapy regimen including platinum or progressed during or after prior a chemotherapy regimen including platinum.	bladder
Robot-Assisted Radical Cystectomy with Intracorporeal Urinary Diversion: A New Standard of Urinary Diversion.	Background: To summarize the current evidence on robot-assisted radical cystectomy (RARC) with intracorporeal urinary diversion (ICUD) and compare perioperative outcomes and postoperative complications of patients undergoing RARC with extracorporeal urinary diversion (ECUD) and ICUD. Patients and Methods: Through a systematical search of multiple scientific databases in March 2020, we performed a systematic review and cumulative meta-analysis of the primary outcomes of interest. Also, we assessed the quality of the relevant evidence according to the framework in the Cochrane Handbook for Systematic Reviews of Interventions. Results: Thirteen studies with 4696 participants were included in this review. No significant differences were found between the ECUD and ICUD in operation time (OT) (mean difference [MD]: -6.45, 95% confidence interval [CI]: -35.20 to 22.30), length of stay (MD: 0.36, 95% CI: -0.81 to 1.54), 30-day overall complications (odds ratio [OR]: 0.92, 95% CI: 0.60-1.41), 30-day minor complications (OR: 1.36, 95% CI: 0.85-2.19), 30-day major complications (OR: 0.70, 95% CI: 0.34-1.43), 90-day overall complications (OR: 1.34, 95% CI: 0.83-2.18), and major complications (OR: 1.03, 95% CI: 0.68-1.57). However, less estimate blood loss (MD: 99.28 mL, 95% CI: 62.59-135.98), lower intraoperative blood transfusion (OR: 1.80, 95% CI: 1.09-2.95), shorter oral intake time (MD: 0.78, 95% CI: 0.43-1.14), and 90-day minor complications (OR: 1.72, 95% CI: 1.08-2.73) were associated with ICUD. The subgroup analysis showed less estimated blood loss (MD: 149.73, 95% CI: 21.33-278.13) and less OT (MD: 32.45, 95% CI: 14.37-50.53) were found in ICUD. Conclusions: The ICUD is a safe and feasible alternative to ECUD, which decreases the need for blood transfusion and reduces 90-day complications. However, further quality studies are needed to evaluate effectiveness of ICUD and its oncologic outcomes, functional outcomes, cost, and the quality of life.	bladder
Significant reduction of indeterminate (atypical) diagnosis after implementation of The Paris System for Reporting Urinary Cytology: A single-institution study of more than 27,000 cases.	BACKGROUND: Urinary cytology is a noninvasive and cost-effective diagnostic and surveillance test in the clinical management of urothelial carcinoma (UC). The Paris System for Reporting Urinary Cytology (TPS), published in 2016, introduced definite diagnostic criteria aimed at improving performance in detecting high-grade UC (HGUC) and decreasing the indeterminate (atypical) diagnosis. METHODS: The authors retrospectively reviewed and compared urinary cytology diagnoses reported between January 2013 and December 2014 (pre-TPS, 7658 cases) and between May 2016 and April 2018 (post-TPS, 20,026 cases) to assess the influence of TPS in their practice. The time in between was used as a learning period. Follow-up information and correlation with the UroVysion fluorescence in situ hybridization test were obtained when available. RESULTS: Urinary cytology diagnoses pre-TPS included negative for UC (NUC) (n = 5293; 69.2%), atypical urothelial cells (AUC) (n = 2227; 29%), and suspicious/positive for HGUC (SHGUC/HGUC) (n = 138; 1.8%). Diagnoses post-TPS included negative for HGUC (NHGUC) (n = 18,507; 92.4%), AUC (n = 1237; 6.2%), and SHGUC/HGUC (n = 282; 1.4%). Comparing the pre-TPS and post-TPS periods, AUC diagnoses decreased from 29% to 6.2% (P < .00001), and the specificity and positive predictive value of AUC to detect HGUC significantly improved from 49% to 86% (P < .00001) and from 9% to 39% (P = .002), respectively. The correlation of an AUC diagnosis with a positive UroVysion test improved from 17% to 38% (P < .00001), whereas overall use of the UroVysion test was decreased. CONCLUSIONS: Implementation of TPS resulted in a significant reduction in AUC diagnoses that had a superior correlation with a subsequent biopsy and a UroVysion test, resulting in potential reductions in test use and medical cost.	bladder
Identification of glycogene-type and validation of ST3GAL6 as a biomarker predicts clinical outcome and cancer cell invasion in urinary bladder cancer.	Background: Urinary bladder cancer (UBC) is one of the most common causes of morbidity and mortality worldwide characterized by a high risk of invasion and metastasis; however, the molecular classification biomarkers and underlying molecular mechanisms for UBC patient stratification on clinical outcome need to be investigated. Methods: A systematic transcriptomic analysis of 185 glycogenes in the public UBC datasets with survival information and clinicopathological parameters were performed using unsupervised hierarchical clustering. The gene signature for glycogene-type classification was identified using Limma package in R language, and correlated to 8 known molecular features by Gene Set Variation Analysis (GSVA). The clinical relevance and function of a glycogene was characterized by immunohistochemistry in UBC patient samples, and quantitative RT-PCR, Western blotting, promoter activity, MAL II blotting, immunofluorescence staining, wound healing, and transwell assays in UBC cells. Results: A 14-glycogene signature for glycogene-type classification was identified. Among them, ST3GAL6, a glycotransferase to transfer sialic acid to 3'-hydroxyl group of a galactose residue, showed a significant negative association with the subtype with luminal feature in UBC patients (n=2,130 in total). Increased ST3GAL6 was positively correlated to tumor stage, grade, and survival in UBCs from public datasets or our cohort (n=52). Transcription factor GATA3, a luminal-specific marker for UBC, was further identified as a direct upstream regulator of ST3GAL6 to negatively regulate its transactivation. ST3GAL6 depletion decreased MAL II level, cell invasion and migration in 5637 and J82 UBC cells. ST3GAL6 could reverse the effects of GATA3 on global sialylation and cell invasion in SW780 cells. Conclusions: Herein, we successfully identified a novel 14-gene signature for glycogene-type classification of UBC patients. ST3GAL6 gene, from this signature, was demonstrated as a potential biomarker for poor outcomes and cell invasion in UBCs.	bladder
Emerging biomarkers in urothelial carcinoma: Challenges and opportunities.	Advanced urothelial carcinoma (UC) is a very important cause of cancer-related morbidity and mortality with, until recently, only a few available therapeutic options. The treatment landscape has dramatically changed in recent years with the introduction of immune checkpoint inhibitors and the development of novel targeted agents, such as erdafitinib, and antibody-drug conjugates, such as enfortumab vedotin. Cost-effective utilization of this rapidly expanding therapeutic armamentarium can be further optimized via the identification and validation of reliable prognostic and predictive biomarkers that inform prognostication and patient selection. In this review, we aim to summarize examples of recent developments in the rapidly expanding field of emerging biomarkers in UC, outlining challenges and opportunities.	bladder
Integrative genomics and pathway analysis identified prevalent FA-BRCA pathway alterations in arsenic-associated urinary bladder carcinoma: Chronic arsenic accumulation in cancer tissues hampers the FA-BRCA pathway.	Arsenic in drinking water is one of the major etiological factors in urinary bladder carcinoma (BlCa). Here, high-resolution CGH-SNP microarray analysis in arsenic accumulated BlCa tissues showed significant (p < 0.05) association of chromosomal alterations with high arsenic (≥112 ng/g) accumulation, further corroborated by high γH2AX nuclear expression. Cytobands 5q11-35, 9p24.3-21.5, 18q11.1-25, etc. showed deletion, whereas 12q was amplified in high arsenic samples (AsH). Consecutively, IPA® found FA-BRCA pathway to be exclusively altered in AsH group. Validation of several key regulatory genes (RAD50, BRIP1, UIMC1, FANCD2, BRCA2 and BRCA1) of the pathway, were performed in independent BlCa cases (n = 81). UIMC1, RAD50 and BRIP1 were differentially deleted and associated with poor survival of AsH samples. Moreover, reduced nuclear expression with diffused cytoplasmic expression of FANCD2 was higher in AsH samples. Collectively, frequent deregulation of RAD50, UIMC1 and BRIP1 may result in reduced nuclear translocation of FANCD2, which may cause more chromosomal aberrations among AsH samples.	bladder